Project Summary Affecting nearly 1 in every 250 children in the United States, juvenile arthritis are the most common chronic illnesses of childhood. In past years, pediatric rheumatology research has made a great deal of progress in knowledge of the outcome assessment and disease management. It is now time to learn more about how to treat and prevent disease- and treatment-related morbidities. Without questioning the usefulness and effectiveness of immunosuppressive treatment for patients with juvenile idiopathic arthritis (JIA), it must be acknowledged that the manipulation of the immune system inherent to these therapies increases the risk of infection for these patients. Infection is one of the leading causes of morbidity and mortality in patients with rheumatic disease. Despite significant advances in pediatric rheumatology research, many questions remain regarding the risk of infection associated with immunosuppressant therapeutic agents commonly used to treat JIA and the published data is inconsistent and inadequately understood. The overall goal of this proposal is to study the safety of common immunosuppressive treatments for pediatric patients with juvenile idiopathic arthritis (JIA) who are at high risk for infections through three Specific Aims. Specific Aim 1 will determine whether juvenile idiopathic arthritis immunosuppressive treatments increase the risk of infections requiring hospitalization (serious infections), ED or outpatient care (non-serious infections). Specific Aim 2 will estimate the degree of infection risk associated with each treatment. Specific Aim 3 will compare infection risk and discontinuation rate for the most commonly prescribed tumor necrosis factor inhibitor (TNFi) agents in JIA to optimize selection of JIA therapy. Our proposed study will capitalize on an existing data set to address pressing knowledge gaps surrounding the relative safety of common JIA-related therapies with regard to hospitalizations and infections. This proposal will improve the quality of pediatric care for patients with rheumatic diseases, while furthering the National Institute of Allergy and Infectious Diseases (NIAID) mission to conduct and support research to better understand, treat, and ultimately prevent infectious diseases. The long-term goal of this research is to identify modalities to decrease infections in pediatric patients with rheumatic diseases by producing evidence-based knowledge. Establishing such methodologies can be used to decrease infections in children with similar complex medical conditions.